We propose to characterize the physical-chemical properties and the biological activity of the cell surface components that we have isolated from mouse cerebral cortex tissue that are capable of inhibiting cellular macromolecular synthesis and replication. Our present data on the inhibitor, purified over 3000-fold, indicates that the inhibitor is a cell surface glycoprotein. Several primary, tissue culture adapted, and tumorigenic cell lines will be used to determine why highly malignant cells are relatively insensitive, or completely refractory to the inhibitory action of the cell surface substance. After further purification by affinity chromatography and isoelectric focusing we will obtain an antibody and prepare radiolabelled monovalent F(ab) fragments. This will provide a sensitive probe to detect and measure the relative amounts of this substance on nontumorigenic and tumorigenic cells. Radiolabelled inhibitor and F(ab) fragments will also be used to measure the quantity of inhibitor bound to sensitive and insensitive cells and to identify the site of action at the subcellular level. Our investigation will include experiments on the phase of the mitotic cycle where the inhibitor arrests cell replication and to pursue our preliminary data that suggests cells eventually escape growth inhibition.